Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: Increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy

Diabetic patients undergoing hyperbaric oxygen treatments (HBO2) for refractory lower extremity neuropathic ulcers exhibit more than a 2-fold elevation (p=0.004) in circulating stem cells after treatments and the post-HBO2 CD34 + cell population contains 2 to 3-fold higher levels of hypoxia inducible factors (HIF)-1, -2 and -3, as well as thioredoxin-1 (p≤0.003) than cells present in blood prior to HBO2. Skin margins obtained from two day old abdominal wounds exhibit higher expression of CD133, CD34, HIF-1 and Trx-1 versus margins from refractory lower extremity wounds and expression of these proteins in all wounds is increased due to HBO2 treatment (p≤0.003). HBO2 is known to mobilize bone marrow stem cells by stimulating nitric oxide synthase (NOS). We found that NOS activity is acutely increased in patient's platelets following HBO2 and remains elevated for at least 20 hours. We conclude that HBO2 stimulates vasculogenic stem cell mobilization from bone marrow of diabetics and more cells are recruited to skin wounds.